2012 Grants - Colby

2012 New Investigator Research Grant

Alzheimer's disease, like many neurological disorders, targets a wide variety of neurons, which are nerve cells in the brain. To better study the progression of this disease, research teams have tried to engineer many different Alzheimer's-influenced cell types in the laboratory. One such engineering method involves taking human cells from the skin and blood and reprogramming them as brain cells. In this method, modified viruses bind to and deliver proteins called transcription factors to cells in the body. The transcription factors can alter the cell's expression and transform them into neurons.

David W. Colby, Ph.D., and colleagues plan to use cell reprogramming to develop many Alzheimer's-related neurons that have not yet been engineered in the laboratory. First, they plan to create a library of about 60 transcription factors that are involved in neuron production. They will then use the transcription factors to reprogram cells obtained from people with Alzheimer's disease. Some of the cells will be engineered into basal forebrain cholinergic neurons (BFCNs), which are important for memory and attention and are affected early in Alzheimer's. The researchers will identify the exact set of transcription factors required to produce BFCNs. They will also test their engineered cells to see if they exhibit the abnormalities characteristic of Alzheimer's—including high levels of toxic beta-amyloid and tau molecules. The results of this work could offer important new tools for studying how Alzheimer's disease targets certain neurons causing injury and cell death.